Cutting Edge: CD8+ T Cell Priming in the Absence of NK Cells Leads to Enhanced Memory Responses

Soderquest, Katrina; Walzer, Thierry; Zafirova, Biljana; Klavinskis, Linda; Polić, Bojan; Vivier, Éric; Lord, Graham M.; Martín-Fontecha, Alfonso

doi:10.4049/jimmunol.1004122

Cited by 126 publications

(132 citation statements)

References 17 publications

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“…Unfortunately, studies of immune responses in NKG2D-deficient mice are complicated by altered NK cell development and function in these animals. NK cells limit effector and memory CD8 T cell expansion in a partially NKG2D-dependent way (18,19). Moreover, NK cells of Klrk1 2/2 mice are hyperresponsive, resulting in enhanced viral clearance on day 4 postinfection (7).…”

Section: Nkg2d Promotes Memory Formation and Antiviral Protectionmentioning

confidence: 99%

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

Wensveen

Lenartić

Jelenčić

et al. 2013

The Journal of Immunology

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Memory formation of activated CD8 T cells is the result of a specific combination of signals that promote long-term survival and inhibit differentiation into effector cells. Much is known about initial cues that drive memory formation, but it is poorly understood which signals are essential during the intermediate stages before terminal differentiation. NKG2D is an activating coreceptor on Ag-experienced CD8 T cells that promotes effector cell functions. Its role in memory formation is currently unknown. In this study, we show that NKG2D controls formation of CD8 memory T cells by promoting survival of precursor cells. We demonstrate that NKG2D enhances IL-15–mediated PI3K signaling of activated CD8 T cells, in a specific phase of memory cell commitment, after activation but before terminal differentiation. This signal is essential for the induction of prosurvival protein Mcl-1 and precursor cell survival. In vivo, NKG2D deficiency results in reduced memory cell formation and impaired protection against reinfection. Our findings show a new role for PI3K and the NKG2D/IL-15 axis in an underappreciated stage of effector to memory cell transition that is essential for the generation of antiviral immunity. Moreover, we provide novel insights how these receptors control both effector and memory T cell differentiation.

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Section: Nkg2d Promotes Memory Formation and Antiviral Protectionmentioning

confidence: 99%

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

Wensveen

Lenartić

Jelenčić

et al. 2013

The Journal of Immunology

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“…It has been reported that NK cells regulate T cell responses through multiple direct and indirect mechanisms, including NK cell-mediated killing of activated CD8 + T cells (14,15,(18)(19)(20)(21), CD4 + T cells (18,19,22,23), and also of dendritic cells (DCs) (12,24,25). However, little is known about a possible NK cell-mediated inhibitory/regulatory role during antitumor immune responses.…”

mentioning

confidence: 99%

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Iraolagoitia

Spallanzani

Torres

et al. 2016

The Journal of Immunology

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Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context of a growing tumor. In this article, we show that NK cells can limit spontaneous cross-priming of tumor Ag-specific CD8+ T cells, leading to reduced memory responses. After challenge with MC57 cells transduced to express the model Ag SIY (MC57.SIY), NK cell–depleted mice exhibited a significantly higher frequency of SIY-specific CD8+ T cells, with enhanced IFN-γ production and cytotoxic capability. Depletion of NK cells resulted in a CD8+ T cell population skewed toward an effector memory T phenotype that was associated with enhanced recall responses and delayed tumor growth after a secondary tumor challenge with B16.SIY cells. Dendritic cells (DCs) from NK cell–depleted tumor-bearing mice exhibited a more mature phenotype. Interestingly, tumor-infiltrating and tumor-draining lymph node NK cells displayed an upregulated expression of the inhibitory molecule programmed death ligand 1 that, through interaction with programmed death-1 expressed on DCs, limited DC activation, explaining their reduced ability to induce tumor-specific CD8+ T cell priming. Our results suggest that NK cells can, in certain contexts, have an inhibitory effect on antitumor immunity, a finding with implications for immunotherapy in the clinic.

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“…Along this line, Soderquest et al (1) reported that NK cells induced apoptosis in recently activated CD8…”

Section: T Cell Priming In the Absence Of Nk Cells Leads To Enhanced mentioning

confidence: 86%

Response to Comment on “Cutting Edge: CD8+ T Cell Priming in the Absence of NK Cells Leads to Enhanced Memory Responses”

Soderquest

Lord

Martín-Fontecha

2011

The Journal of Immunology

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Cutting Edge: CD8+ T Cell Priming in the Absence of NK Cells Leads to Enhanced Memory Responses

Cited by 126 publications

References 17 publications

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Response to Comment on “Cutting Edge: CD8+ T Cell Priming in the Absence of NK Cells Leads to Enhanced Memory Responses”

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